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Blood, 1 November 2005, Vol. 106, No. 9, pp. 2995-3003. Prepublished online as a Blood First Edition Paper on July 19, 2005; DOI 10.1182/blood-2004-12-4906. This Article Full Text (PDF) All Versions of this Article: 2004-12-4906v1 106/9/2995    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Moeller, M. Articles by Darcy, P. K Search for Related Content PubMed PubMed Citation Articles by Moeller, M. Articles by Darcy, P. K Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 23, 2004 Accepted July 5, 2005 Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection Maria Moeller, Nicole M Haynes, Michael H Kershaw, Jacob T Jackson, Michele W Teng, Shayna E Street, Loretta Cerutti, Stephen M Jane, Joseph A Trapani, Mark J Smyth, and Phillip K Darcy* Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA, USA Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Parkville, Victoria, Australia * Corresponding author; email: phil.darcy{at}petermac.org. Since CD4+ T cells play a key role in aiding cellular immune responses, we wanted to assess whether increasing numbers of gene-engineered antigen-restricted CD4+ T cells could enhance an anti-tumor response mediated by similarly gene-engineered CD8+ T cells. In this study, we have used retroviral transduction to generate erbB2-reactive mouse T cell populations composed of various proportions of CD4+ and CD8+ cells, and then determined the anti-tumor reactivity of these mixtures. Gene-modified T cells were shown to specifically secrete Tc1 and/or Tc2 cytokines, proliferate and lyse erbB2+ tumor targets following antigen ligation in vitro. In adoptive transfer experiments using immunodeficient scid mice we demonstrated that injection of equivalent numbers of antigen-specific engineered CD8+ and CD4+ T cells led to significant improvement in survival of mice bearing established lung metastases compared with transfer of unfractionated (largely CD8+) engineered T cells. Transferred CD4+ T cells had to be antigen-specific (not just activated) and secrete IFN- to potentiate the anti-tumor effect. Importantly, anti-tumor responses in these mice correlated with localisation and persistence of gene-engineered T cells at the tumor site. Strikingly, mice that survived primary tumor challenge could reject a subsequent rechallenge. Overall, this study has highlighted the therapeutic potential of using combined transfer of antigen-specific gene-modified CD8+ and CD4+ T cells to significantly enhance T cell adoptive transfer strategies for cancer therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Jing, J. A. Gershan, and B. D. Johnson Depletion of CD4 T cells enhances immunotherapy for neuroblastoma after syngeneic HSCT but compromises development of antitumor immune memory Blood, April 30, 2009; 113(18): 4449 - 4457. [Abstract] [Full Text] [PDF] H. Wang, H. Wei, R. Zhang, S. Hou, B. Li, W. Qian, D. Zhang, G. Kou, J. Dai, and Y. Guo Genetically Targeted T Cells Eradicate Established Breast Cancer in Syngeneic Mice Clin. Cancer Res., February 1, 2009; 15(3): 943 - 950. [Abstract] [Full Text] [PDF] P. C.R. Emtage, A. S.Y. Lo, E. M. Gomes, D. L. Liu, R. M. Gonzalo-Daganzo, and R. P. Junghans Second-Generation Anti-Carcinoembryonic Antigen Designer T Cells Resist Activation-Induced Cell Death, Proliferate on Tumor Contact, Secrete Cytokines, and Exhibit Superior Antitumor Activity In vivo: A Preclinical Evaluation Clin. Cancer Res., December 15, 2008; 14(24): 8112 - 8122. [Abstract] [Full Text] [PDF] Z. Liu, H. S. Noh, J. Chen, J. H. Kim, L. D. Falo Jr., and Z. You Potent Tumor-Specific Protection Ignited by Adoptively Transferred CD4+ T Cells J. Immunol., September 15, 2008; 181(6): 4363 - 4370. [Abstract] [Full Text] [PDF] M. Moeller, M. H. Kershaw, R. Cameron, J. A. Westwood, J. A. Trapani, M. J. Smyth, and P. K. 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